title: Low-dose aspirin vs low-dose aspirin plus low-intensity warfarin in thromboprophylaxis: a prospective, multicentre, randomized, open, controlled trial in patients positive for antiphospholipid antibodies (ALIWAPAS).
abstract: OBJECTIVE
  The objectives of this study are to examine the efficacy and safety of low-dose aspirin (LDA) vs LDA plus low-intensity warfarin (LDA + W) in the primary thrombosis prevention of aPL-positive patients with SLE and/or obstetric morbidity and the role of clinical and serological markers in the development of thrombosis.
  
  
  METHODS
  In this 5-year prospective, randomized, open, controlled trial, 166 patients with aPL were randomly assigned using a minimization protocol to receive treatment with LDA (n = 82) or LDA + W [international normalized ratio (INR) = 1.5] (n = 84). Sixty-six patients who declined randomization were followed up in an observational arm. Clinical and laboratory characteristics and medication side effects were recorded.
  
  
  RESULTS
  There were no differences in the number of thromboses between patients treated with LDA (4/82) or LDA + W (4/84) [hazard ratio (HR) 1.07, 95% CI 0.27, 4.3]. The incidence of thrombosis in the randomized patients was 8/166 (1.8 events/100 person-years) (HR 1.07, 95% CI 0.27, 4.3) and in the observational arm was 7/66 (4.9 events/100 person-years) (HR 2.43, 95% CI 0.87, 6.79). Sixty-five of 66 patients included in the observational arm received LDA. None of the examined clinical or serological factors appeared to predict thrombosis. Medication side effects included mild gastrointestinal symptoms in the LDA group (n = 2) and bleeding in the LDA + W group (n = 11; 1 nasal and 10 menorrhagia). The risk difference for bleeding was 13% (CI 6, 20).
  
  
  CONCLUSIONS
  No differences in the number of thromboses were observed between patients treated with LDA vs those treated with LDA + W. More episodes of bleeding were detected in the LDA + W group. The LDA + W regime was significantly less safe and not as acceptable as LDA alone.
  
  
  BACKGROUND
  ISRCTN81818945; http://isrctn.org/.
authors.affiliation: Lupus Research Unit, Rayne Institute, St Thomas' Hospital, London SE1 7EH, UK. mjcuadrado@yahoo.com.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Cuadrado
authors.forename: Maria L
authors.initials: ML
authors.lastname: Bertolaccini
authors.forename: Paul T
authors.initials: PT
authors.lastname: Seed
authors.forename: Maria G
authors.initials: MG
authors.lastname: Tektonidou
authors.forename: Angeles
authors.initials: A
authors.lastname: Aguirre
authors.forename: Luisa
authors.initials: L
authors.lastname: Mico
authors.forename: Caroline
authors.initials: C
authors.lastname: Gordon
authors.forename: Guillermo
authors.initials: G
authors.lastname: Ruiz-Irastorza
authors.forename: Maria V
authors.initials: MV
authors.lastname: Egurbide
authors.forename: Antonio
authors.initials: A
authors.lastname: Gil
authors.forename: Gerard
authors.initials: G
authors.lastname: Espinosa
authors.forename: Frederic
authors.initials: F
authors.lastname: Houssiau
authors.forename: Anisur
authors.initials: A
authors.lastname: Rahman
authors.forename: Helena
authors.initials: H
authors.lastname: Martin
authors.forename: Neil
authors.initials: N
authors.lastname: McHugh
authors.forename: Maria
authors.initials: M
authors.lastname: Galindo
authors.forename: Mohammed
authors.initials: M
authors.lastname: Akil
authors.forename: Mary C
authors.initials: MC
authors.lastname: Amigo
authors.forename: Veronica
authors.initials: V
authors.lastname: Murru
authors.forename: Munther A
authors.initials: MA
authors.lastname: Khamashta
mesh_terms: D000328:Adult; D017152:Antibodies, Antiphospholipid / Q000097:blood* / Q000276:immunology; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000150:complications / Q000276:immunology; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000097:blood / Q000150:complications / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000276:immunology*; D011446:Prospective Studies; D013927:Thrombosis / Q000276:immunology / Q000517:prevention & control*; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D017152:Antibodies, Antiphospholipid; D000925:Anticoagulants; D014859:Warfarin; D001241:Aspirin
keywords: antiphospholipid antibodies; thromboprophylaxis; treatment